Periodontal disease can have serious consequences to human health. Briefly, periodontal disease is characterized by the loss of the connective tissue structures and bone below the gum line. It typically results in the formation of a so-called periodontal pocket exceeding about 3 mm in depth, and inflammation. It is caused by the accumulation of bacteria and other microbes in the crevice (sulcus) between the gum and a tooth, and usually occurs after the onset of gingivitis.
The disease of periodontitis can cause the tissues connecting the gum to the teeth to deteriorate, resulting in the loss of supporting attachment to the associated tooth and subsequent tooth loss, often times accompanied by halitosis. In addition to these localized effects, medical studies have found an association between periodontal disease and adverse effects in other parts of the body, such as cardiovascular disease, diabetes, and premature births. A strong need therefore exists to provide an effective treatment to eradicate (kill) the bacteria and other microbes that cause periodontal disease.
Three approaches for treating periodontal disease have included (A) the time-released application of an antibiotic, (B) the time-released application of chlorahexadine, an antimicrobial agent, and (C) lavaging with a solution containing an antibacterial agent such as povidone iodine. Each of these approaches suffers serious drawbacks as the following shows.
A. Antibiotics
Antibiotics are antimicrobial agents that are derived from living organisms, such as bacteria or fungus. Typical antibiotics selectively kill only certain types of bacteria, and not other types. Thus, an antibiotic might not kill all the types of malignant bacteria that cause periodontal disease, thereby impairing its effectiveness. Secondly, bacteria may become resistant to the antibiotic, further impairing its effectiveness. With these serious drawbacks in mind, two antibiotic products that have been sold in the US are described.
An ATRIDOX® pharmaceutical delivery system comprises a time-released antibiotic, doxycycline contained in a liquid carrier that is injected into the periodontal pocket. The carrier solidifies so that it can remain in the periodontal pocket for a sustained duration, and allows the release of doxycycline over a sustained period of time, typically over a period of 3-4 days. The liquid carrier is prepared from a two-component mixture. Once solidified, the carrier cannot again be liquefied and reused, so that each time a patient is treated, a new batch of carrier must be prepared. Additionally, the antibiotics used suffer the drawbacks described above.
An ARESTIN® medication-dispensing device uses the antibiotic minocycline that is prepared in the form of a powder. It is inserted into the periodontal pocket with a carpule which is a tube-like device having a plunger. The powdered antibiotic dissolves over time to kill bacteria, but often does not remain localized in the periodontal pocket. This reduces its effectiveness to the disease in the pocket. The antibiotic also suffers from the drawbacks described above.
B. Chlorahexadine—Antimicrobial Agent
The PERIO CHIP™ sustained release polymer device comprises a small, gelatin-based carrier and medicament of the anti-microbial agent chlorahexadine in the form of a wafer. The wafer is inserted into the periodontal pocket, and dissolves over a small period of time so as to release chlorahexadine. One drawback to using chlorahexadine is that its antimicrobial action is inhibited by the presence of blood. Because bleeding is common in a diseased periodontal pocket, the effectiveness of chlorahexadine is diminished. Another disadvantage of using the PERIO CHIP™ is that it uses gelatin as a carrier for the anti-microbial agent. The “chip” must be kept refrigerated when not in use because when it is inserted into the periodontal pocket of the patient, it will begin to dissolve at the internal temperature of the patient's mouth. As such, the gelatinized “chip” won't be sustained within the pocket for a length of time, usually less than 24 hours, that will enable the active ingredient to completely treat the diseased pocket. An inefficiency therefore accompanies this approach since multiple “chip” treatments are required.
C. Povidone Iodine—Antibacterial Agent
The medicament povidone iodine is effective on a broad spectrum of bacteria, and does not appear to cause the formation of strain-resistant bacteria as do antibiotics. It is also non-staining to the teeth. It is effectively used for short-term treatments, and its antibacterial action is not inhibited by the presence of blood. Typically, a dentist will prepare an aqueous solution of povidone iodine to lavage, or wash, the periodontal pocket.
However, owing to the liquid nature of the solution containing the povidone iodine, the solution quickly drains from the periodontal pocket. This compels a dentist to apply a considerable quantity of solution (e.g., 20 cc's) in a single visit by the patient. The procedure typically takes approximately 2-3 minutes. Unfortunately, the administration of a considerable quantity of solution incurs the risk of the patient inadvertently swallowing the povidone iodine solution. The drawback of this approach is that it can harm the patient since the ingestion of too much povidone iodine can cause toxic reaction in the body. For instance, the thyroid gland can become abnormally enlarged, causing the gland to produce too much thyroid hormone, which in turn, can cause adverse affects throughout the body, and in severe reactions, death. Other toxic effects include swelling of the throat or stomach, swelling or paralysis of the esophagus, and asphyxiation from swelling of the larynx.
As indicated above, the lavaging procedure using a povidone iodine solution takes approximately 2 to 3 minutes during which time the liquid solution will quickly drain from the periodontal pocket. In order to make the administration of the povidone iodine effective, a dentist will use it in a relatively high concentration of the solution, e.g., 10% by volume. Such a high concentration exacerbates the problem and risk of a patient inadvertently ingesting the solution.
Accordingly, it is desirable to provide a composition and method for effectively delivering a medicament, such as povidone iodine, to the periodontal pocket over a period of time, i.e., for a minimum time of treatment of 24 hours, preferably 1 to 3 days, in order to bring about the result of (i) effectively and substantially eliminating bacteria in the periodontal pocket that causes the periodontal disease as well as decreasing microbial flora; (ii) reducing the size of the periodontal pocket caused by the periodontal infection; (iii) retaining and increasing attachment of the affected gum(s) to the tooth or teeth, as the case may be; (iv) decreasing accompanying bleeding; and (v) substantially avoiding toxic reaction in the body due to inadvertent ingestion of the medicament by the patient over a short period of time.
These and other objects are accomplished by various embodiments of the invention which are described in detail as follows.